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Application of PPAR[gamma] to influence liver cancer by promoting terminal differentiation of MMP9<+> tumor-associated macrophages

A cell and liver cancer treatment technology, applied in the field of biomedicine

Active Publication Date: 2021-11-23
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the therapeutic application of TAMs is still in its infancy, and TAM-related therapeutic strategies offer only modest clinical benefits

Method used

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  • Application of PPAR[gamma] to influence liver cancer by promoting terminal differentiation of MMP9&lt;+&gt; tumor-associated macrophages
  • Application of PPAR[gamma] to influence liver cancer by promoting terminal differentiation of MMP9&lt;+&gt; tumor-associated macrophages
  • Application of PPAR[gamma] to influence liver cancer by promoting terminal differentiation of MMP9&lt;+&gt; tumor-associated macrophages

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 MMP9 + TAMs ratio increased in hepatocellular carcinoma, and significantly correlated with poor prognosis

[0037] To explore the role of MMP9 + TAMs in hepatocarcinogenesis First, we download TCGA hepatocellular carcinoma (TCGA-LIHC) from Broad FireHose (http: / / gdac.broadinstitute.org / ) queue primary tumor and non-tumor data and clinical data standardization gene expression in liver tissue. Tumor or tumor liver tissue abundance subtype one cell marker gene by the sum of all gene expression data to estimate the number of conversions for a large number of RNA sequences. To evaluate the relationship between the composition of the non-malignant cells and prognosis, we will one kind of subset of cells divided by abundance of all HCC patients dataset identified single cells and stromal cells types share immune abundance sum, it standardization. We Cox proportional hazards model analysis revealed that tumor MMP9 + TAM closely related (HR = 1.5, P = 0.03 and TCGA-LIHC qu...

Embodiment 2

[0039] Example 2 MMP9 + TAMs promote the invasion of hepatoma cells, migration and angiogenesis

[0040] In order to study the role of MMP9 + TAMs in HCC in progress, we collected fresh tumor tissue and corresponding cancer, a single cell solution from the days of the US-ni instrument will organize dissociated into single cell suspension, dead cells using magnetic beads adsorption remove dead cells, after the method of flow-sorted isolated CD45 + CD68 + CD11b- macrophages from primary tumors, and isolated from the whole population of macrophages in non-tumor liver (CD45 + CD68 +) as a control . The sorting out of the cells labeled with viable cell stain LM3 cells coinoculated contacting co-cultured for 16 hours in the absence of Matrigel and Transwell chambers with a matrigel explore MMP9 + TAMs LM3 migration in hepatoma cell lines and Invasion effect. like image 3 (A-b), as compared with the two control groups, sorted MMP9 + TAMs significantly promotes cell migration and invasion...

Embodiment 3

[0042] Example 3 After knockdown PPARγ embodiment THP1 cells into MMP9 + TAMs proportional reduction

[0043] To explore MMP9 + TAMs PPAR [gamma] is a transcription factor inducing differentiation, we first method lentivirus infection stable knockdown PPAR [gamma] construct (sequence see Table 1) in THP1 cells. like Figure 4 As shown, we will stabilize and knock control cells THP1 cells were treated with low PPARγ PMA 24 hours induced THP1 cells M0 tumor macrophages, LM3 after co-cultured with non-contact hepatoma cells for 48 hours at the same time, the medium was replaced HCC-CM 1640 is a mixture of medium and induced to become TAM-like cells, the proportional flow analysis and detection of MMP9 + TAMs.

[0044] ShRNA sequence information table of 1.PPARγ

[0045]

[0046] like Figure 5 (A), we used CD45 + CD68 + CD11b + denoted MMP9 + TAMs, THP1 found after induction of PPARγ MMP9 + TAMs knockdown ratio (33.1%) was significantly lower than the control group (50.5%). like Figu...

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Abstract

The invention relates to the field of biological medicine, in particular to application of PPAR gamma to influence liver cancer by promoting terminal differentiation of MMP9 <+> tumor-associated macrophages. Research results show that the proportion of MMP9+ TAMs in liver cancer tissues is increased and is significantly related to poor prognosis of patients; further experimental results show that PPAR gamma promotes deterioration of liver cancer by inducing differentiation of MMP9 + TAMs; after the PPAR gamma is knocked down or knocked out, the proportion of inducing THP1 cells into MMP9 + TAMs is reduced, and after the PPAR gamma is knocked down or knocked out, the proportion of inducing PBMC cells into MMP9 + TAMs is reduced; after THP1 cells of which PPAR gamma is knocked down or knocked out are induced into TAMs, the migration, invasion and tube forming capabilities of liver cancer cells are reduced; and after the PBMC with the PPAR gamma knocked down or knocked out is induced into TAMs, the migration, invasion and tube forming capabilities of the liver cancer cells are reduced.

Description

Technical field [0001] The present invention relates to the field of biomedicine, and in particular, PPARγ affects the application of liver cancer by promoting the end differentiation of MMP9 + tumor-related macrophages. Background technique [0002] Tumor-related macrophages (TAMS) are present in a tumor microenvironment, which is the main component of white intracellular filtrate. Due to its important role in tumor, development and metastasis, TAMS is increasingly being regarded as an important target in a tumor microenvironment. TAMS can promote tumor progression through a variety of mechanisms, including inducing angiogenesis, extracellular matrix remodeling, stimulating cancer cell proliferation, migration, and invasion, and inhibiting adaptive immunity. However, the endogenous regulation mechanism of tumor-related macrophage differentiation is still unclear. [0003] TAMS expression promotes breast cancer, prostate cancer, cervical cancer, and ovarian cancer generation and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574C12Q1/02A61K45/00A61P35/00A61P35/04
CPCG01N33/57438G01N33/5029G01N33/502A61K45/00A61P35/00A61P35/04
Inventor 周钢桥杨爱清卢一鸣权诚
Owner ACADEMY OF MILITARY MEDICAL SCI
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